Heart is innervated by both sympathetic and parasympathetic divisions of the autonomic nervous system. Release of norepinephrine from postganglionic sympathetic nerves activates β1-adrenoceptors in the heart, notably on the sion-atrial (SA) node, atrioventricular (AV) node, His-Purkinje conductive tissue, and atrial and ventricular contractile tissue. In response to stimulation of sympathetic nerves, the heart rate (chronotropy), rate of transmission in the cardiac conducive tissue (dormitory), and the force of ventricular contraction (inotropy) are increased.
On the other hand, release of acetylcholine from postganglionic parasympathetic (vagus) nerves activates nicotinic receptors in the heart, notably on the SA and AV nodes and atrial muscle. In response to stimulation of the vagus nerve, the heart rate, the rate of transmission through the AV node, and atrial contractility are reduced.
Besides, there are adrenergic and cholinergic receptors on autonomic nerve terminals that modulate transmitter release from nerve endings. For example, releases of acetylcholine from vagal nerve terminals inhibits the release of norepinephrine from sympathetic nerve terminals, so this enhance the effects of vagal nerve activation on the heart.
The Cardiac Cycle
The Cardiac Output
Predictably, changes in cardiac output that are called for by physiologic conditions can be produced by changes in cardiac rate, or stroke volume, or both.
End-diastolic ventricular volume, in health person it is usually about 130 mL.
End-systolic ventricular volume, in health person it is usually about 50 mL.
Ejection fraction = stroke volume/end-diastolic ventricular volume, in health person it is usually about 65%.
The cardiac rate is controlled primarily by the autonomic nerves, with sympathetic stimulation increasing the rate and parasympathetic stimulation decreasing it. Stroke volume is also determined in part by neural input, with sympathetic stimuli making the myocardial muscle fibres contract with greater strength at any given length and parasympathetic stimuli having the opposite effect. When the strength of contraction increases without an increase in finer length, more of the blood that normally remains in the ventricles is expelled.
The force of contraction of cardiac muscle also depends on its preloading and its afterlaoding. These factors are illustrated in the figure on the left. A muscle strip is stretched by a load (the preload) that rests on a platform. The initial phase of the contraction is isometric; the elastic component in series with the contractile element is stretched, and tension increases until it is sufficient to lift the load. The tension at which the load is lifted is the afterload. The muscle then contracts isotonically without developing further tension. In vivo, the preload is the degree to which the myocardium is stretched before it contracts and the afterload is the resistance against which blood is expelled.
Cardiac muscle has cross-striations, but it is functionally syncytial and, although it can be modulated via the autonomic nervous system, it can contract rhythmically in the absence of external innervation owing to the presence in the myocardium of pacemaker cells that discharge spontaneously.
Muscular contraction involves shortening of the contractile elements, but because muscles have elastic and viscous elements in series with the contractile mechanisms, it is possible for contraction to occur without an appreciable decrease in the length of the whole muscle. Such a contraction is called isometric. Contraction against a constant load with a decrease in muscle length is isotonic. Note that because work is the product of force times distance, isotonic contractions do not work, whereas isometric contractions do not. In other situations, muscle can do negative work while lengthening against a constant weight.
The influence of muscle length on the behavior of the cardiac muscle during isometric contraction is illustrated in Figure 2-8. The top panel shows the experimental arrangement for measuring muscle force at rest and during contraction at three different lengths. The middle Panel shows time records of muscle tensions recorded at each of the three lengths in response to an external stimulus, and the bottom panel shows a graph of the resting and peak tension results plotted against muscle length.
The first important fact illustrated in Figure 2-8 is that force is required to stretch a resting muscle to different lengths. This force is called the resting tension. The lower curve in the graph in Figure 2-8 shows the resting tension measured at different muscle lengths and is referred to as the resting length-tension curve. When a muscle is stimulated to contract while its length is held constant, it develops an additional component of tension called active or developed tension. The total tension exerted by a muscle during contraction is the sum of the active and resting tensions.
The second important fact illustrated in Figure 2-8 is that the active tension developed by the cardiac muscle during the course of an isometric contraction depends very much on the muscle length at which the contraction occurs. Active tension development is maximal at some intermediate length referred to as Lmax. Little active tension is developed at very short or very long muscle lengths. Normally, the cardiac muscle operates at lengths well below Lmax so that increasing muscle length increases the tension developed during an isometric contraction.
During what is termed isotonic contraction (the load is fixed), a muscle shortens against a constant load. A muscle contracts isotonically when it develops sufficient tension to lift a fixed weight such as 1-g load shown in Figure 2-9. Such a 1-g weight placed on a resting muscle will result in some specific resting muscle length, which is determined by the muscle’s resting long-tension curve. If the ends of the muscle were to be fixed between two immoveable objects and the muscle were to be activated at this fixed length, it would contract isometrically and be capable of generating a certain amount of tension, for example, 4.5 g as indicated by the dashed line in the graph in Figure 2-9. A contractile tension of 4.5 g obviously cannot be generated if the muscle is allowed to shorten and actually lift the 1-g weight. When a muscle has contractile potential in excess of the tension required to move the load, it will shorten. Thus, in an isotonic contraction, muscle length decreases at constant tension, as illustrated by the horizontal arrow from point 1 to point 3 in Figure 2-9. As the muscle shortens, however, its contractile potential inherently decreases, as indicated by the downward slope of the peak isometric tension curve in Figure 2-9. There exists some short length at which the muscle is capable of generating only 1 g of tension, and when this length is reached, shortening must cease. Therefore, the peak isometric curve on a cardiac muscle length-tension diagram also establishes the limit on how far muscle shortening can proceed with different loads.
Figure 30-5 illustrate three important factors that alter cardiac output, including preload, and contractility, heat rate, and afterload. It should be always remembered in mind that cardiac out is the result of the integrated control of those mechanisms discussed below.
Preload affects the cardiac output by Frank-Starling law. For the heart the length of the muscle fibres (preload) is proportional to the end-diastolic volume. When the muscle is stretched, the developed tension increases to a maximum and then declines as stretch becomes more extreme. Figure 5-18 show the principle of Frank-Starling law. Several factors can affect the cardiac output via preload, including,
1.An increase in intrapericardial pressure limits the extent to which the ventricle can fill.
2.A decrease in ventricular compliance limits the extent to which the ventricle can fill. This condition consists of increase in ventricular stiffness produced by myocardial infarction, infiltrative disease, and so on.
3.Atrial contractions (the “atrial kick”) aid ventricular filling. Especially in elderly people the atrial kick contribute significantly to the ventricular filling.
4.Factors affecting the amount of blood returning to the heart likewsie change the ventricular filling during diastole. For instance, an increase in total blood volume increases venous return. Constriction of the veins reduces the size of the venous reservoirs, decreasing venous pooling and thus increasing venous return. An increase in the normal negative intrathoracic pressure increase the pressure gradient along which blood flows to the heart, where a decrease impedes venous return. Standing decreases venous return, and muscular activity increases it as a result of the pumping action of skeletal muscle.
Someone summarised the factors affecting ventricle filling, including 1.the filling pressure of blood returning to the heart and artia;2.the ability of the AV valves to open fully;and 3.the ability of the ventricular wall to expand passively with little resistance (compliance).
The ANS affects the contractility directly via neurotransmitters, with sympathetic nerves increasing the contractility and parasympathetic nerves decreasing it.
Circulating neurohormonals affects heart contractility in the same way like the ANS, with catecholamines increasing the contractility and acetylcholine decreasing it.
Change of heart rate and rhythm also contribute to contractility as discussed below.
Heart increases the cardiac out obviously because the cardiac out equals the stroke multiplying the heart rate (CO = SV * HR). Heart rate is influenced by ANS directly. Circulating neurohormones also contribute to the accelerate or decelerate the heart rate. However, if the heart rate is too fast, the time used to ventricular filling is compromised, and as a result the ventricular end-diastolic volume is reduced, which causes: 1.preload is compromised; 2.the heart starts to eject blood while the ventricle is not properly filled enough.
Changes in cardiac rate and rhythm also affect myocardial contractility, know as the force-frequency relation. Ventricular extrasystoles condition the myocardium in such a way that the next succeeding contraction is stronger than the preceding normal contraction. This postextrasystolic potentiation is independent of ventricular filling, since it occurs in isolated cardiac muscle and is due to increased availability of intracellular Ca2+. Also while the heart rate increases, the myocardial contractility increases, although the increment is relatively small.
Figure 2-9 shows a complex type of muscle contraction that is typical of the way cardiac muscle cells actually contract in the heart. This is called an after loaded isotonic contraction, in which the load on the muscle at rest (the preload) and the load on the muscle during contraction (the total load) are different. In the example of Figure 2-9, the preload is equal to 1 g, and because an additional 2-g weight (the afterload) is engaged during contraction, the total load equals 3 g.
Because preload determines the resting muscle length, both contractions shown at top of Figure 2-9 begin from the same length. Because of the different loading arrangement, however, the after loaded muscle must increase its total tension to 3 g before it can shorten. This initial tension will be developed isometrically and can be represented as going from point 1 to point 4 on the length-tension diagram. Once the muscle generates enough tension to equal the total load, its tension output if fixed at 3 g and it will now shorten isotonically because its contractile potential still exceeds its tension output. This isotonic shortening is represented as a horizontal movement on the length-tension diagram along the line from point 4 to point 5. As in any isotonic contraction, shortening must cease when the muscle’s tension-producing potential is decreased sufficiently by the length change to be equal to the load on the muscle.
So, it is very clear that the afterload limits the degree at which the cardiac muscle can shorten maximally.
Systemic Regulation by Nuerohumoral Agents
Many circulating substances affect the vascular system. The vasodilator regulators include kinins, VIP (vasoactive intestinal polypeptide), and ANP (atrial natriuretic peptide/natriuretic hormones). Circulating vasoconstrictor hormones include vasopressin, norepinephrine, epinephrine, and angiotensin II.
Two related vasodilator peptides called kinins are found in the body. One is the nonapeptide bradykinin, and the other is the decapeptide lysylbradykinin, also known as kallidin. The action of both kinins resemble those of histamine. They are primarily paracrines, although small amounts are also found in the circulating blood. They cause contraction of visceral smooth muscle, but they relax vascular smooth muscle via NO, lowering blood pressure. They also increase capillary permeability, attract leukocytes, and cause pain upon injection under the skin.
They are formed during active secretion in sweat glands, salivary glands, and the exocrine portion of the pancreas, and they are probably responsible for the increase in blood flow when these tissues are actively secreting their products.
Vasoactive Intestinal Peptide
Also known as the vasoactive intestinal polypeptide or VIP is a peptide hormone containing 28 amino acidresidues. VIP is neuropeptide that belongs to a glucagon/secretin superfamily, the ligand of class II G protein-coupled receptors. VIP is produced in many tissues of vertebrates including the gut, pancreas, and suprachiasmatic nuclei of the hypothalamus in the brain. VIP stimulates contractility in the heart, causes vasodilation, increases glycogenolysis, lowers arterial blood pressure and relaxes the smooth muscle of trachea, stomach and gall bladder.
There is a family of natriuretic peptides involved in vascular regulation, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). ANP and BNP are secreted by the heart, where the muscle cells in the atria and, to a lesser extent, in the ventricles contain secretory granules. They are also present in human brain. They are released in response to hypervolemia. ANP secretion is increased when ECF volume is increased and the atria are stretched. BNP secretion is increased when the ventricles are stretched.
PS: ANP secretion is also increased by immersion in water up to the neck, a procedure that counteracts the effect of gravity on the circulation and increases central venous and consequently atrial pressure.
ANP and BNP circulate, whereas CNP acts predominantly in a paracrine fashion. In general, these peptides antagonise the action of various vasoconstrictor agents and lower blood pressure due to relax vascular smooth muscle in arterioles and venules. Natriuretic hormones have other actions including to increase the permeability of capillary, leading to extravasation of fluid and a decline in blood pressure.
In the brain, ANP is present in neurons, and an ANP-containing neural pathway projects from the anteromedial part of the concerned with neural regulation of the cardiovascular system. ANP’s effects are generally opposite to those of angiotensin II. BNP and CNP in the brain probably have similar function as ANP.
In the kidneys, ANP and BNP also serve to coordinate the control of vascular tone with fluid and electrolyte homeostasis. Specifically, ANP and BNP in the circulation act on the kidneys to increase fluid and Na+ excretion and injected CNP has a similar effect. They appear to produce this effect by dilating afferent arterioles and relaxing mesangial cells. Both of these actions increase glomerular filtration. In addition, they act on the renal tubules to inhibit Na+ reabsorption.
PS: ANP: atrial natriuretic peptide (ANP), BNP: brain natriuretic peptide, and CNP: C-type natriuretic peptide.
Vasopressin is a potent vasoconstrictor, but when it is injected in normal individuals, there is a compensating decrease in cardiac output, so that there is little change in blood pressure. Vasopressin’s main function is to regulate the ECF volume, see http://www.tomhsiung.com/wordpress/2014/03/the-regular-of-extracellular-fluids-adh-secretion-and-renin-angiotensin-system/.
Norepinephrine has a generalized vasoconstrictor action, whereas epinephrine dilates the vessels in skeletal muscle and the liver, see http://www.tomhsiung.com/wordpress/2015/01/the-regulation-of-circulation-central-mechanisms/.
Angiotensin II has a generalized vasoconstrictor action of angiotensin converting enzyme (ACE) on angiotensin I, which itself is liberated by the action of renin from the kidney on circulating angiotensinogen. See http://forum.tomhsiung.com/pharmacy-practice/pharmacotherapy/640-regulation-ecf-body.html for the factors affecting production of Angiotensin II.
Urotensin-II, a polypeptide first first isolated from the spinal cord of fish, is present in human cardiac and vascular tissue. It is one of the most potent mammalian vasoconstrictors known, and is being explored for its role in a large range of different human disease states. For example, levels of both urotensin-II and its receptor have been shown to be elevated in hypertension and heart failure, and may be marker of disease in these and other conditions.
See thread The Autoregulation of Renal Blood Flow http://www.tomhsiung.com/wordpress/2014/06/the-autoregulation-of-renal-blood-flow/
The metabolic changes that produce vasodilation include, in most tissues, decreases in O2 tension and pH. These changes cause relaxation of the arterioles and pre capillary sphincters.
A local fall in O2 tension, in particular, can initiate a program of vasodilatory gene expression secondary to production of hypoxia-inducible factor-1α (HIF-1α), a transcription factor with multiple targets.
Increased in CO2 tension and osmolality also dilate the vessels. The direct dilator action of CO2 is most pronounced in the skin and brain.
A rise in temperature exerts a direct vasodilator effect, and the temperature rise in active tissues (due to the heat of metabolism) may contribute to the vasodilation.
K+ is another substance that accumulates locally, and has demonstrated dilator activity secondary to the hyperpolarization of vascular smooth muscle cells.
Lactate may also contribute to the dilation.
In injured tissues, histamine released from damaged cells increases capillary permeability. Thus, it is probably responsible for some of the swelling in areas of inflammation.
Adenosine may play a vasodilator role in cardiac muscle but not in skeletal muscle. It also inhibits the release of norepinephrine.
Injured arteries and arterioles constrict strongly. The constriction appears to be due in part to the local liberation of serotonin from platelets that stick to the vessel wall in the injured area. Injured veins also constrict.
A drop in tissue temperature causes vasoconstriction, and this local response to cold plays a part in temperature regulation.